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3D Bioprinting Strategies for Melatonin-Loaded Polymers in Bone Tissue Engineering
(Wiley-V C H Verlag Gmbh, 2025) Aykora, Damla; Oral, Ayhan; Aydeger, Cemre; Uzun, Metehan
Bone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer-based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell-derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next-generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer-based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well-known antioxidant with many osteoinductive properties and is one of the key hormones in the brain-bone axis. 3D bioprinted melatonin-loaded polymers with unique lipophilic, anti-inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches.
Adalimumab mitigates ovarian ischemia-reperfusion injury in rats by regulating oxidative stress, apoptosis and resolution of inflammation
(Wiley, 2019) Beyazit, Fatma; Buyuk, Basak; Turkon, Hakan; Elmas, Sait; Uzun, Metehan
Aim Ovarian torsion is a rare but an important reason of acute lower abdominal pain in women and associated with serious morbidity and mortality, if not treated promptly. The aim of this study was to evaluate the effects of an antitumor necrosis factor-alpha antibody on ovarian torsion in a rat model of ischemia-reperfusion (I/R) injury. Methods Forty female Wistar Albino rats were used in the present study. The rats were randomly divided into four groups: group I (sham), group II (I/R), group III (I/R + isotonic saline) and group IV (I/R + adalimumab). The I/R model was induced by torsion of both ovaries. Immunohistochemical staining for interleukin-1 beta (IL-1 beta), nuclear factor-kappa B (NF-kappa B), and inducible nitric oxide synthase was performed. Tissue and serum oxidative stress markers in conjunction with apoptotic index (AI) with the terminal deoxynucleotidyl transferase dUTP nick end labeling method were also calculated. Results Tissue total oxidant status, oxidative stress index and nitric oxide values were significantly decreased, and tissue total antioxidant status was found to be increased in group IV. Inflammation, vascular congestion and hemorrhagia were significantly lower in adalimumab-treated group. Serum oxidative stress markers and tissue malondialdehyde levels did not differ in study groups. The AI was significantly increased in groups 2 and 3. Adalimumab treatment significantly decreased the AI. Conclusion Adalimumab therapy in rats attenuated I/R induced ovarian injury, possibly suppressing inflammation, inhibiting oxidative stress, and altering apoptotic pathways.
Akut Yorucu Egzersiz Yaptırılan Sıçanlarda Melatoninin Elektrokardiyografik Veriler Üzerindeki Etkilerinin Araştırılması
(2021) Uzun, Metehan; Cakan, Pinar
Amaç: Akut yorucu egzersiz kardiyovasküler sistem (KVS) için ilave bir yük oluşturmaktadır. Melatonin ise KVS üzerine koruyucu etkileri olduğu\rbilinen bir hormondur. Bu çalışma ile akut yorucu egzersiz uygulanan sıçanlarda KVS’de meydana gelen değişikliklerin elektrokardiyografi (EKG)\rverileri üzerinden değerlendirilmesi ve melatoninin koruyucu etkilerinin araştırılması amaçlandı.\rGereç ve Yöntem: Çalışma 3-5 aylık 28 adet Wistar Albino sıçan üzerinde yürütüldü ve 4 ayrı grup oluşturuldu. Kontrol grubuna sadece taşıyıcı\rçözelti uygulandı ve herhangi bir egzersiz yapılmadı. Egzersiz, egzersiz+melatonin (egzersizden önce 10 mg/kg intraperitonal melatonin enjeksiyonu)\rve egzersiz+melatonin+luzindole (egzersizden önce intraperitonal 0,4 mg/kg dozda luzindol ve 10 mg/kg melatonin enjeksiyonu) grupları 5-25 m/\rdk hızda koşu bandında yoruluncaya kadar koşturuldu. Egzersiz sonrasında EKG verileri kaydedildi.\rBulgular: EKG verilerine göre, her iki egzersiz grubunda kalp hızının anlamlı düzeyde arttığı belirlendi. Melatonin uygulamasının egzersiz grubunda\ranlamlı düzeyde artan QT ve QTc süresi uzamalarını kısalttığı, luzindol verilen grupta ise melatoninin bu etkisinin ortaya çıkmadığı belirlendi.\rMelatonin aynı zamanda egzersizle artan kortikosteron seviyelerini reseptör bağımsız bir şekilde azalttı. Egzersizle artan akyuvar sayısı ve nötrofil\rdüzeyleri melatonin grubunda kontrol grubuna yakın düzeyde belirlendi.\rSonuç: Bu sonuçlar melatoninin, egzersizde ortaya çıkabilecek istenmeyen etkileri azaltıcı ve egzersiz kalitesini artırıcı bir ajan olarak kullanılabileceğini\rgöstermektedir
Bone tissue engineering for osteointegration: Where are we now?
(Springer, 2024) Aykora, Damla; Uzun, Metehan
Bone fracture healing is a challenging process, due to insufficient and slow tissue repair. Sufferers from bone fractures struggle with one-third of nonunion, display graft rejection, high-costed implantation, or chronic pain. Novel advances in tissue engineering presented promising options for this strain. Biomaterials for bone repair allow accelerated regeneration, osteoblastic cell activation, and enhanced bone remodeling. There is a wide range of biomaterials that are biocompatible, bioresorbable, and biodegradable and used for bone tissue regeneration, promoting osteoconductive and osteoinductive properties. The main aim of bone tissue engineering is to generate rapid and optimal functional bone regeneration through a combination of biomaterials, growth factors, cells, and various agents. Recently bone tissue engineering has been attracted to the use of bioactive glass scaffolds incorporated with polymers and patient-specific fabrication of the bone healing material by 3D bioprinting. There are promising future outcomes that were reported by several research. The present review provides an outlook for recent most common biomaterials in bone tissue engineering suggesting bone tissue engineering practices should have been proceeded to clinical application.
Comparison of the effects of various airway devices on hemodynamic response and QTc interval in rabbits under general anesthesia
(Springer Heidelberg, 2015) Toman, Huseyin; Erbas, Mesut; Sahin, Hasan; Kiraz, Hasan Ali; Uzun, Metehan; Ovali, Mehmet Akif
In this study, we aimed to compare the effects of various airway devices on QTc interval in rabbits under general anesthesia. The subjects were randomly separated into four groups: Group ETT, Group LMA, Group PLA, Group V-gel. Baseline values and hearth rate, mean arterial pressure and ECG was obtained at the 1st, 5th and 30th minutes after administration of anesthesia and placement of airway device and, QTc interval was evaluated. Difference was observed between ET group and V-gel group in the 5th minute mean arterial pressure values (p < 0.05). It was observed that QTc intervals at the 1st and 5th minute in the ET group significantly increased when compared with the other groups (p < 0.05). Again, it was observed that QTc interval of ET group at the 15th and 30th minute was longer when compared with PLA and V-gel groups (p < 0.05). It was also observed that QTc interval of LMA Group at the 5th minute after intubation significantly increased when compared with V-gel group (p < 0.05). It was observed that HR values of ETT group at the 1st, 5th and 15th minutes after intubation increased with regards to PLA and V-gel groups (p < 0.05). It was determined that the 30th minute hearth rate of ETT group was higher when compared to V-gel group (p < 0.05). Conclusion: In our study we observed that V-gel Rabbit affected both hemodynamic response and QT interval less than other airway devices.
Development of melatonin-embedded PLGA-PEG6000 nanofiber biomaterial, and investigation of the effects on abdominal adhesion formation
(SAGE Publications Ltd, 2024) Gökçe, Oruç Numan; Aykora, Damla; Danışman, Merve; Demir, Ufuk; Aydeğer, Cemre; Süner, Salih Can; Oral, Ayhan; Karaboğa, İhsan; Uzun, Metehan
Abdominal adhesions are still among the most common postsurgical peritoneal inflammation-related complications. Adhesion-related disorders are still highly costly and prevalent due to advances in surgical techniques, treatment methods, and various drugs. The present study aimed to investigate the effects of Poly (D,L-lactide-co-glycolide) (PLGA)- polyethylene glycol (PEG6000) Nanofiber + Melatonin on the abdominal adhesion model in rats. For this purpose, PLGA-PEG6000 Nanofiber + Melatonin matrix was fabricated and implanted in an experimental abdominal adhesion model in rats. Our study consisted of an in vitro and an in vivo part. The degradation and release profile of the matrix and Melatonin (Mel) embedded matrix was performed in vitro. In vivo, the procedure was carried out with 18 Wistar male rats. Rats were divided into three groups as follows: Sham, Matrix, and Mel + Matrix, respectively. Consequent to degradation and release profiling in vitro, an experimental adhesion model was created and fabricated pure matrix (2 × 2 cm2), and matrix (2 × 2 cm2, 0.25 mg melatonin/per matrix embedded) was applied to injury area in related groups. Intra-abdominal adhesion scores were determined on post-op 21st day, under general anesthesia. Following, cecum, peritoneal tissue, and adhesive bands were harvested. Macroscopic analysis (severity of adhesion formation), Hematoxlyn&Eosin and Masson’s Trichrome staining (for the examination of the levels of infiltration of inflammatory cells, fibrosis, and neovascularization) were performed for the evaluation of the effects of Mel embedded and pure matrix Our results indicated that PLGA-PEG6000 Nanofiber + Melatonin matrix was degraded completely in rats abdominal cavity and significantly reduced adhesion formation compared to other groups macroscopically (p < 0.05). On the other hand, the histopathological analysis indicated that the fabricated matrix reduced inflammatory cell infiltration, fibrosis, and neovascularization levels.
Effects of High Levels of Copper Supplementation to the Diet on some Blood Values and Thyroid Hormones in Japanese Quails (Coturnix coturnix japonica)
(Kafkas Univ, Veteriner Fakultesi Dergisi, 2011) Onder, Feyyaz; Cenesiz, Metin; Kaya, Mehmet; Uzun, Metehan; Karademir, Guler
In this study was aimed to determine the effects of high levels of copper supplementation on some blood values and thyroid hormones in Japanese quails (Coturnix coturnix japonica). It was used totally 64 Japanese quail (one-day-old) as material in the study. Chicks were divided into four groups and they were given 0 mg/kg (control, group I), 100 mg/kg (group II), 250 (group III) and 500 mg/kg (group IV) copper in addition to their concentrate for 40 days. There were no difference hematocrit value, leukocyte number, differential leukocyte number, serum thyroid stimulating hormone (TSH) and free triiodothyronine levels (FT3) between the groups (P > 0.05). Serum copper levels were enhanced in copper supplemented groups (group II, III, IV) (P < 0.05). Copper supplementation to diet was induced to reduce the serum free thyroxine and erythrocyte number in all experimental groups (group II, III, IV) (P < 0.05). Hemoglobin amount were enhanced significantly (P < 0.05) in groups III and IV compared with control group and group II. It was induced to reduce in weight gain the 500 mg/kg Cu supplementation to the diet in compared with other groups (P < 0.05). As a result, the findings obtained from in this study is important that in terms of to reveal effects of excessive copper on thyroid hormones and to be used as a source prospective investigations.
Effects of Melatonin on Aquaporin Channels in Isoproterenolinduced Myocardial Infarction in Rats
(Galenos Publ House, 2023) Tufekcioglu, Nezahat Kubra; Buyuk, Basak; Uzun, Metehan
Aim: Myocardial infarction (MI) commonly results in myocardial edema, but the relationship between aquporin channels (AQP) and the effects of melatonin (MEL) on MI are not well known. Therefore, the aim of the current study was to investigate the effects of MEL on myocardial edema and the change of gene expression level of AQP channels in an experimental MI model. Materials and Methods: In this study 28 Wistar Albino male rats were used. MI model was established with isoproterenol (85mg/kg). Rats were divided into four groups as: control, isoproterenol (ISO), melatonin (MEL), and isoproterenol+melatonin (ISO+MEL). MEL group was administered 10 mg/kg MEL for 7 days. On day 8, electrocardiographic recordings and blood samples were obtained. Rats were then euthanized and left ventricle tissues were obtained. cTnI and CK-MB levels were examined to assess the success of MI model. AQP1, AQP3, AQP4, AQP7, TNF-alpha, BAX and Caspase-3 gene expression levels were determined. Histopathological examination was performed on left ventricle samples for the evaluation of edema and mononuclear cellular infiltration. Results: Histopathological examination and cTnl and CK-MB levels showed that MI model was produced successfully and MEL significantly reduced myocardial edema and decreased AQP1, AQP3, AQP4 and AQP7 gene expression levels. Conclusion: The results show that MEL decreases myocardial edema by reducing AQP channels, suggesting that it could potentially be used to ameliorate the effects of MI.
Effects of Melatonin on Blood Pressure, Oxidative Stress and Placental Expressions of TNF?, IL-6, VEGF and sFlt-1 in RUPP Rat Model of Preeclampsia
(Elsevier Science Inc, 2017) Uzun, Metehan; Gencer, Meryem; Turkon, Hakan; Oztopuz, Rahime Ozlem; Demir, Ufuk; Ovali, Mehmet Akif
[Anstract Not Available]
Genetic variability in the prion protein gene in five indigenous Turkish sheep breeds
(Elsevier, 2011) Alvarez, Lorena; Gutierrez-Gil, Beatriz; Uzun, Metehan; San Primitivo, Fermin; Jose Arranz, Juan
Ovine susceptibility to scrapie is largely controlled by polymorphisms in the PRNP gene. Beginning in 2003, breeding programmes based on the known association between this gene and the susceptibility/resistance status of this disease have been implemented in many European countries. This is not the case in Turkey, where the PRNP gene was not genotyped in native sheep breeds until recently. We sequenced the complete open reading frame of the PRNP gene in 100 sheep belonging to five native Turkish sheep breeds (Akkaraman = 21; Morkaraman = 20; Tuj = 17; Hemsin = 23; Karayaka = 19). Based on the variability found at codons 136, 154 and 171 (also referred to as standard codons), we determined six alleles VRQ TRQ ARR, ARH, ARK and ARQ. The archetype, ARQ was the most frequent variant in each of the five breeds (across-breed frequency = 0.710), while the second most frequent was the resistance-associated ARR allele (0.140). The susceptible VRQ allele exhibited the lowest frequency (0.015). The AHQ allele was not found in any of the analysed breeds. Beyond variability in the standard codons, we found ten additional amino acid variants (M112T, G127S, G127V, M137T, L141F, H143R, N146S, Y172D, Q189L and V213E), one of which, V213E, has not been previously described to our knowledge. Overall, this report may serve as a complement of previous studies on the genetic background of native Turkish sheep regarding the resistance/susceptibility status to classical and atypical scrapie. (C) 2011 Elsevier B.V. All rights reserved.
Humic Acid Has Protective Effect on Gastric Ulcer by Alleviating Inflammation in Rats
(Pleiades Publishing Inc, 2022) Sehitoglu, Muserref Hilal; Oztopuz, Ozlem; Karaboga, Ihsan; Ovali, Mehmet Akif; Uzun, Metehan
The new agents are needed in treatment of gastric ulcer that have less side effects, adequate efficacy, and no drug interactions. In this study, we aimed to investigate the potential protective effects of humic acid on experimental gastric ulcer. Wistar Albino male rats (n = 48) were randomly divided into 8 groups as follow; Control (without any applications), Humic acid (50 mg/kg), ethanol group (1 mL/rat), and indomethacin group (25 mg/kg). In the treatment groups, both gastric ulcer model and humic acid 50 mg/kg were applied. In addition, famotidine the antiulcer drug was used as positive control. All medications were administered by oral gavage. Levels of ADAM10 and ADAMTS12 in gastric mucosa were determined by ELISA method. Hematoxylin-Eosin (H&E) staining, iNOS, and PCNA immunohistochemical staining were performed for histopathological investigations. Apoptosis was demonstrated by using the TUNEL method. In addition, the levels of inflammatory cytokines (TNF-alpha, IL-6, IL-10) and caspase-3 gene were determined by qRT-PCR. ADAM10 and ADAMTS12 levels significantly increased in the treatment groups compared to the ulcer groups (p < 0.05). The experimental groups showed mucosal erosion, bleeding, leukocyte infiltration and edema. Treatment with humic acid and famotidine was found to suppress iNOS activity, thereby decreasing proinflammatory activity and preventing damage to the gastric mucosa, while reducing the number of apoptotic cells. IL-6, IL-10, TNF-alpha and caspase-3 levels were significantly decreased in the treatment groups compared to damaged gastric mucosa. As a result, humic acid may be defined as a potential protective agent with its anti-inflammatory effect in gastric ulcer.
Hyperbaric oxygen treatment ameliorates gentamicin-induced nephrotoxicity and expression of kidney injury molecule 1 in the rat model
(Undersea & Hyperbaric Medical Soc Inc, 2019) Oztopuz, Ozlem; Turkon, Hakan; Sehitoglu, Muserref Hilal; Buyuk, Basak; Uzun, Metehan; Ovali, Mehmet Akif; Demir, Ufuk
In recent years, hyperbaric oxygen (HBO2) therapy has been considered as an effective method for the treatment of gentamicin (GM)-induced renal toxicity. However, the findings related to the use of HBO2 for GM toxicity are limited and contradictory. The aim of this study is to investigate the protective role of HBO2 on GM-induced nephrotoxicity. For this purpose, Wistar albino rats (n=28) were randomly divided into four equal groups: C, HBO2, GM and GM+HBO2. GM (100 mg/kg, ip) and HBO2 were applied over seven days. On the eighth day blood and kidney tissue samples were harvested. The albumin, creatinine, and urea levels were determined from serum samples. Superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) activities, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) values were analyzed spectrophotometrically. The relative expression level of TNF-alpha, IL-1 beta and Kim-1 gene were determined by qRT-PCR assays; histopathologic investigation was completed in kidney tissue samples. Serum urea, albumin and creatinine levels significantly increased in the GM group compared to the GM+HBO2 group. For antioxidant parameters the GM+HBO2 group was not statistically different from the C group but was significantly different compared with the GM group. TNF-alpha, IL-1 beta and Kim-1 gene expression levels in the GM group were statistically increased compared to the GM+HBO2 group (p=0.015, p=0.024, p=0.004) respectively. Severe tubular necrosis, epithelial desquamation and mild peritubular hemorrhage were observed in the GM-administrated group, while HBO2 exposure ameliorated these alterations. In conclusion, HBO2 exposure may be defined as a potential method for the prevention of GM-induced renal toxicity.
Investigation of the Effects of Melatonin on Aquaporin Channels in Isoproterenol-Induced Myocardial Infarction Model
(Wiley, 2022) Tufekcioglu, Nezahat Kubra; Uzun, Metehan
[Anstract Not Available]
Investigation of the Effects of Piceatannol on Endoplasmic Reticulum Stress on Brain in Rats with Experimental Subarachnoid Hemorrhage
(Galenos Publ House, 2024) Ozbey, Berna; Uzun, Metehan
Aim: Subarachnoid hemorrhage (SAH) is a common neurologic disorder that accounts for brain injury, diminished neuron function, and neuronal death. Due to various options, SAH treatment remains lacking. Endoplasmic reticulum stress (ERS) in the brain is known as the disruption of the blood-brain barrier and triggered neuronal apoptosis, and contributes to SAH pathogenesis. This study aims to investigate the effects of piceatannol (PST) on ERS and neuronal apoptosis in an experimental SAH model in rats. Materials and Methods: For this purpose, 24 Wistar Albino male rats (8-10 w) were randomly divided into three groups (n=8); SHAM, SAH, and PST. SAH model was induced via injection of 120 mu L of autologous blood into pre-chiasmatic cisterna. 30 mg/kg PST was injected intraperitoneally after 60 minutes from SAH inducement. Garcia's neurologic examination, rotarod, and horizontal bar tests were applied for neurological evaluation. Frontal cortex specimens were harvested for histological and gene expression analysis. Results: Our results indicated that PST treatment significantly improved Garcia scores (p<0.01; p<0.05). In addition, PST decreased pyknosis (p<0.001) and edema (p<0.001) levels, and the number of damaged cells (p<0.01) and apoptotic cells (p<0.05). GRP78 (78-kDa glucose-regulated protein; p=0.01), ATF4 (Activating transcription factor 4; p=0.01), and CHOP (C/EBP homologous protein; p<0.05) gene expression levels of the SAH group were increased compared to SHAM. Moreover, PST significantly decreased the expression levels of p53 (p<0.01). Conclusion: Our results showed that PST indicated protective effects on ERS after SAH. It could be suggested that PST might be a supportive adjuvant agent in SAH management.
Investigation of the protective effects of L-carnitine and L-arginine on cardiovascular changes induced by ACTH and dexamethasone in rabbits
(Tubitak Scientific & Technological Research Council Turkey, 2013) Topcu, Birkan; Uzun, Metehan
Aim: To determine the protective effects of L-carnitine on cardiovascular changes that may occur in rabbits treated with adrenocorticotropic hormone (ACTH) and dexamethasone (DEX). Materials and methods: Rabbits of equal weight were divided into 7 groups with 6 animals in each. Blood samples were collected from all groups on days 1, 7, and 14, and blood pressure values and ECG monitoring were recorded. Nitric oxide (NO), creatine kinase MB (CK-MB), and troponin I (TnI) levels were determined in blood samples. Heart rate, QT, and corrected QT (QTc) values were calculated from ECG records. Results: The QT and QTc times were prolonged significantly (P < 0.001) in the ACTH-treated groups compared to the control group, and L-carnitine had no protective effect. Moreover, CK-MB (P < 0.05) and TnI (P < 0.001) levels were higher in the ACTH-treated groups than they were in the control group. Conclusion: Application of ACTH results in prolongation of QT and QTc intervals and increases in GK-MB and TnI levels, which are indicators of heart muscle damage.
Investigation of the protective effects of piceatannol on experimental subarachnoid hemorrhage in rats
(Springer, 2024) Erbil, Guelfem; Uzun, Metehan
Background Subarachnoid hemorrhage (SAH) is one of the most prevalent brain injuries in humans which has poor prognosis and high mortality rates. Due to several medical or surgical treatment methods, a gold standard method doesn't exist for SAH treatment. Piceatannol (PCN), a natural analog of resveratrol, was reported to reduce inflammation and apoptosis promising a wide range of therapeutic alternatives. In this study, we aimed to investigate the effects of PCN in an experimental SAH model. The alleviating effects of PCN in the hippocampus in an experimental SAH model were investigated for the first time. Methods and results In this study, 27 Wistar Albino male rats (200-300 g; 7-8 week) were used. Animals were divided into three groups; SHAM, SAH, and SAH + PCN. SAH model was created with 120 mu l of autologous arterial tail blood to prechiasmatic cisterna. 30 mg/kg PCN was administered intraperitoneally at 1st h after SAH. Neurological evaluation was performed with Garcia's score. RT-PCR was performed for gene expression levels in the hippocampus. Pyknosis, edema, and apoptosis were evaluated by H&E and TUNEL staining. Our results indicated that PCN administration reduced apoptosis (P < 0.01), cellular edema, and pyknosis (P < 0.05) in the hippocampus after SAH. Moreover, PCN treatment significantly decreased the expression levels of TNF-alpha (P < 0.01), IL-6 (P < 0.05), NF-kappa B (P < 0.05), and Bax (P < 0.05) in the hippocampus. Conclusions Our results demonstrated that PCN might be a potential therapeutic adjuvant agent for the treatment of early brain injury (EBI) following SAH. Further studies are required to clarify the underlying mechanisms and treatment options of SAH.
Japon bıldırcınlarında (Coturnix coturnix japonica) rasyona yüksek düzeylerde bakır ilavesinin tiroit hormonları ve bazı kan değerleri üzerine etkisi
(2011) Önder, Feyyaz; Çenesiz, Metin; Kaya, Mehmet; Uzun, Metehan; Karademir, Güler
Bu araştırmada Japon bıldırcınlarında (Coturnix coturnix japonica) rasyona yüksek düzeylerde bakır ilavesinin tiroit hormonları vebazı kan değerleri üzerine etkilerinin belirlenmesi amaçlanmıştır. Araştırmada materyal olarak 1 günlük toplam 64 Japon bıldırcınıkullanıldı. Civcivler 4 gruba ayrıldı ve 40 gün süreyle 0 mg/kg (kontrol, grup I), 100 mg/kg (grup II), 250 mg/kg (grup III) ve 500 mg/kg(grup IV) bakır ilave edilen rasyonla beslendi. Hematokrit değer, akyuvar sayısı, akyuvarların yüzde oranı, serum tiroit uyarıcı hormon(TSH) ve serbest triiyodotironin (ST3) düzeyleri gruplar arasında farklılık göstermedi (P>0.05). Serum bakır düzeyleri bakır ilave edilengruplarda (grup II, III, IV) arttı (P<0.05). Rasyona bakır ilavesi bütün deneme gruplarında (grup II, III, IV) alyuvar sayısı ve serum serbest$ST_4$ düzeylerinde azalmaya (P<0.05) neden oldu. Hemoglobin miktarı kontrol grubu ve grup II ile karşılaştırıldığında grup III ve grup IV’teönemli bir şekilde (P<0.05) arttı. Rasyona 500 mg/kg bakır ilavesi grup IV’te, diğer gruplarla karşılaştırıldığında canlı ağırlık kazancındaazalmaya neden oldu (P<0.05). Sonuç olarak, bu araştırmada elde edilen veriler, bakır fazlalığının tiroit hormonları üzerine etkileriniortaya koyması ve ileride yapılacak araştırmaları kaynak teşkil etmesi bakımından önemlidir.
Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats
(Springer, 2020) Oztopuz, Ozlem; Turkon, Hakan; Buyuk, Basak; Coskun, Ozlem; Sehitoglu, Muserref Hilal; Ovali, Mehmet Akif; Uzun, Metehan
Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Therefore, the present study designed to investigate the probable protective role of melatonin against VPA-induced liver toxicity. For that purpose, 28 Wistar rats were randomly selected and divided into four groups, namely the Group C (vehicle), VPA (500 mg/kg/day VPA), MEL + VPA (10 mg/kg/day melatonin + 500 mg/kg/day VPA) and MEL (10 mg/kg/day melatonin). The agents were given by oral gavage for 14 days. Blood and liver tissue samples from all the rats were harvested on the 15th day of experiment. Biochemical analyses were conducted on the blood samples. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), alpha glutathione S-transferases (alpha-GST), nuclear factor-kappa B (NF-kappa B), myeloperoxidase (MPO) and changes in gene expression were examined in the liver tissues. Also, liver histopathological analyses were conducted. VPA administration significantly increased the levels of alpha-GST, MDA, NF-kappa B and of IL-1 beta, TNF-alpha gene expression in the liver compared to Group C. Moreover, vacuolization, hydropic degeneration, inflammatory cell infiltration, and sinusoidal congestion were commonly detected in the VPA-treated group along with the highest apoptotic index (TUNEL staining) values. Melatonin administration was revealed to exhibit powerful protective properties at cellular, inflammatory and oxidative level activities against VPA-induced liver toxicity. Therefore, melatonin administration may be used as an adjuvant therapy against to VPA-induced liver toxicity.
Melatonin attenuates caspase-dependent apoptosis in the thoracic aorta by regulating element balance and oxidative stress in pinealectomised rats
(Canadian Science Publishing, 2019) Doganlar, Zeynep Banu; Uzun, Metehan; Ovali, Mehmet Akif; Dogan, Ayten; Ongoren, Gulin; Doganlar, Oguzhan
The aim of this study was to explain the possible mechanisms by which melatonin deficiency results in cardiovascular injury and to investigate the effects of melatonin administration on important signalling pathways and element equilibrium in the thoracic aorta (TA). For this purpose, we analysed the cellular and molecular effects of melatonin deficiency or administration on oxidative stress, DNA damage, molecular chaperone response, and apoptosis induction in TA tissues of pinealectomised rats using ELISA, RAPD, qRT-PCR, and Western blot assays. The results showed that melatonin deficiency led to an imbalance in essential element levels, unfolded or misfolded proteins, increased lipid peroxidation, and selectively induced caspasedependent apoptosis in TA tissues without significantly affecting the Bcl-2/BAX ratio (2.28 in pinealectomised rats, 2.73 in pinealectomised rats treated with melatonin). In pinealectomised rats, the genomic template stability (80.22%) was disrupted by the significantly increased oxidative stress, and heat shock protein 70 (20.96-fold), TNF-alpha (1.73-fold), caspase-8 (2.03-fold), and caspase-3 (2.87-fold) were markedly overexpressed compared with the sham group. Melatonin treatment was protective against apoptosis and inhibited oxidative damage. In addition, melatonin increased the survivin level and improved the regulation of element equilibrium in TA tissues. The results of the study indicate that melatonin deficiency induces TNF-alpha-related extrinsic apoptosis signals and that the administration of pharmacological doses of melatonin attenuates cardiovascular toxicity by regulating the increase in the rate of apoptosis caused by melatonin deficiency in TA tissue of Sprague-Dawley rats.
Melatonin Improves Left Ventricular Mitochondrial Dynamics in Rats
(Pleiades Publishing Inc, 2022) Uzun, Metehan; Oztopuz, Ozlem; Eroglu, Huseyin Avni; Doganlar, Oguzhan; Doganlar, Zeynep Banu; Ovali, Mehmet Akif; Demir, Ufuk
There is increasing awareness that efficient and regular mitochondrial dynamics improvement cardiac function and affects the quality of life. Melatonin is a main pineal gland hormones and ameliorates mitochondrial dynamics in many cardiac disorders. For that purpose, we administrated melatonin to healthy rats all day long in order to investigate change in left ventricle mitochondrial dynamics both in the end of the nighttime and daytime. Twenty male Wistar rats (3-4 months age) were randomly assigned into Control (C; n = 10) and Melatonin groups (MEL; 10 mg/kg melatonin added drinking water, n = 10). On the 5th day of the study, 5 rats from the groups were randomly selected and euthanized at 08:00 AM and the remaining 5 rats were euthanized at 20:00 PM from each groups and samples of left ventricle (LV) tissue were harvested. Quantitative real-time PCR and western blot analysis demonstrated that melatonin acts preventive role on mitochondrial fusion and mitophagy through the DRP1/FIS1 and BNIP3/NIX axis, respectively. Additionally, melatonin administration significantly reduced P21 activation, induced cell cycle arrest, P27, finally regulated caspase-depended mitochondrial apoptosis signals in a time dependent manner. Our results suggest that melatonin may emerge as a therapeutic candidate to protect the bioenergetic dynamics of mitochondria in hearth.

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